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Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study.

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اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      Antineoplastic Agents/*administration & dosage ; Blood-Brain Barrier/*radiation effects ; Brain Neoplasms/*drug therapy ; Brain Neoplasms/*radiotherapy ; Drug Therapy/*methods ; Magnetic Resonance Imaging/*methods ; Ultrasonography/*methods; Adult ; Aged ; Animals ; Antineoplastic Agents/pharmacokinetics ; Doxorubicin/administration & dosage ; Doxorubicin/analogs & derivatives ; Doxorubicin/pharmacokinetics ; Feasibility Studies ; Female ; Glioma/drug therapy ; Glioma/radiotherapy ; Humans ; Magnetic Resonance Imaging/adverse effects ; Male ; Middle Aged ; Molecular Targeted Therapy/methods ; Polyethylene Glycols/administration & dosage ; Polyethylene Glycols/pharmacokinetics ; Temozolomide/administration & dosage ; Temozolomide/pharmacokinetics ; Ultrasonography/adverse effects ; Young Adult
    • نبذة مختصرة :
      The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to demonstrate safety and feasibility of MRgFUS BBB opening with systemically administered chemotherapy in patients with glioma in a phase I, single-arm, open-label study. Five patients with previously confirmed or suspected high-grade glioma based on imaging underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to their scheduled surgical resection. Samples of "sonicated" and "unsonicated" tissue were measured for the chemotherapy by liquid-chromatography-mass spectrometry. Complete follow-up was three months. The procedure was well-tolerated, with no adverse clinical or radiologic events related to the procedure. The BBB within the target volume showed radiographic evidence of opening with an immediate 15-50% increased contrast enhancement on T1-weighted MRI, and resolution approximately 20 hours after. Biochemical analysis of sonicated versus unsonicated tissue suggest chemotherapy delivery is feasible. In this study, we demonstrated transient BBB opening in tumor and peritumor tissue using non-invasive low-intensity MRgFUS with systemically administered chemotherapy was safe and feasible. The characterization of therapeutic delivery and clinical response to this treatment paradigm requires further investigation.
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    • Grant Information:
      R01 EB003268 United States EB NIBIB NIH HHS
    • Molecular Sequence:
      ClinicalTrials.gov NCT02343991
    • الرقم المعرف:
      0 (Antineoplastic Agents)
      0 (liposomal doxorubicin)
      3WJQ0SDW1A (Polyethylene Glycols)
      80168379AG (Doxorubicin)
      YF1K15M17Y (Temozolomide)
    • الموضوع:
      Date Created: 20190125 Date Completed: 20200624 Latest Revision: 20200624
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC6344541
    • الرقم المعرف:
      10.1038/s41598-018-36340-0
    • الرقم المعرف:
      30674905